Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. CONCISE COMMUNICATION High prevalence of bevirimat resistance mutations in protease inhibitor-resistant HIV isolates Jens Verheyen a , Chris Verhofstede b , Elena Knops a , Linos Vandekerckhove b , Axel Fun c , Diede Brunen c , Kenny Dauwe b , Annemarie M.J. Wensing c , Herbert Pfister a , Rolf Kaiser a and Monique Nijhuis c Objective: Bevirimat is the first drug of a new class of antivirals that hamper the maturation of HIV. The objective of this study was to evaluate the sequence variability of the gag region targeted by bevirimat in HIV subtype-B isolates. Methods: Of 484 HIV subtype-B isolates, the gag region comprising amino acids 357 – 382 was sequenced. Of the patients included, 270 were treatment naive and 214 were treatment experienced. In the latter group, 48 HIV isolates harboured mutations associated with reverse transcriptase inhibitor resistance only, and 166 HIV isolates carried mutations associated with protease inhibitor resistance. Results: In the treatment-naive patient population, approximately 30% harboured an HIV isolate with at least one mutation associated with a reduced susceptibility to bevirimat (H358Y, L363M, Q369H, V370A/M/del and T371del). In HIV isolates with protease inhibitor resistance, the prevalence of bevirimat resistance mutations increased to 45%. Accumulation of mutations at four positions in the bevirimat target region, S368C, Q369H, V370A and S373P, was significantly observed. Mutations associated with bevirimat resistance were detected more frequently in HIV isolates with three or more protease inhibitor resistance mutations than in those with less than three protease inhibitor mutations. Conclusion: Reduced bevirimat activity can be expected in one-third of treatment-naive HIV subtype-B isolates and significantly more in protease inhibitor-resistant HIV. These data indicate that screening for bevirimat resistance mutations before administration of the drug is essential. ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2010, 24:669–673 Keywords: bevirimat, cleavage sites, gag p2, protease inhibitor resistance Introduction Selection of resistance to antiretroviral drugs remains a major obstacle to achieving sustainable suppression of viral replication in HIV-infected patients. Cross-resist- ance between antiretroviral drugs sharing the same target in the HIV replication cycle can lead to an important reduction in the number of therapeutic options. The a Institute of Virology, University of Cologne, Cologne, Germany, b AIDS Reference Laboratory, Ghent University, Ghent, Belgium, and c Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. Correspondence to Jens Verheyen, MD, Institute of Virology, University of Cologne, Fu ¨ rst-Pu ¨ ckler Street 56, 50935 Cologne, Germany. Tel: +49 211 4783927; fax: +49 211 4783927; e-mail: jens.verheyen@uk-koeln.de Received: 28 April 2009; revised: 16 July 2009; accepted: 30 July 2009. DOI:10.1097/QAD.0b013e32833160fa ISSN 0269-9370 Q 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins 669